Infection by Shiga toxin-producing Escherichia coli (STEC) has been associated with enteric diseases since 1983, when Riley et al. reported the isolation of Escherichia coli O157:H7 in patients with haemorrhagic colitis associated with ingestion of undercooked hamburgers (J Clin Microbiol 1983; 18 (3): 512-20). That same year, Karmali et al. reported an association between STEC infection and haemolytic uremic syndrome (HUS) (J Infect Dis 1985; 151 (5): 775-82). Tests carried out in animal models as well as in vitro describe different virulence mechanisms. However, it has been proposed that the most important mechanism is the production of a potent cytotoxin, encoded by a bacteriophage, designated Shiga toxin (Stx). Human, animal or food STEC strains may produce Stx1, Stx2 or variants of Stx1 or Stx2, alone or as a combination of two or more toxins (Stx1/Stx2, Stx1/Stx2v, Stx1c/Stx2, Stx1c/Stx2d, Stx2/Stx2v) (Strockbine et al., Infect. Immun. 1986; 53: 135-40; Friedrich et al., J. Clin. Microbiol. 2003; 41: 2448-53).
The amino acid sequence of Stx1 is identical to that of Shigella dysenteriae Shiga toxin and Stx2 shows 58% sequence homology to Stx1. They carry a 60 MDa plasmid (pol57), involved in the expression of adherence fimbria (EHEC fimbria) and an RTX toxin designated EHEC enterohaemolysin (EHEC-Hly), which is associated with severe disease in humans (Schmidt H. et al., 1995; Infect Immun 1995; 63 (3): 1055-61). It has been suggested that a protease encoded by this plasmid (EspP) would act as an additional virulence factor.
Like enteropathogenic E. coli, STEC carries a chromosomal gene designated eae encoding a protein designated intimin. This protein would be responsible of an intimate attachment of the bacteria to enterocytes and disorganization of microvilli, with production of an A/E lesion (attachment and effacement). Strains carrying the intimin gene and producing Stx2, are associated to severe disease in humans.
An infection by Shiga toxin-producing Escherichia coli is not only characterized by its aggressiveness and virulence, but is also responsible for severe enteric diseases in humans. It produces bloody diarrhea, and serious complications thereof may cause blood, renal and even brain cell damage leading to HUS. The toxins cause damage on the large intestine mucous lining and, if absorbed into the bloodstream, may affect other organs, such as kidneys.
The haemolytic uremic syndrome (HUS) is a generalized thrombotic microangiopathy, mainly accompanied by haemolytic anemia and varying degrees of renal failure. Currently, acute stage mortality ranges from 2.5 to 4%. Of all children affected, 55% become cured, 5% never regain normal renal function, suffering from different degrees of proteinuria and/or arterial hypertension, and the remaining 35% evolves to chronicity, after varying time periods.
At present, the treatment of HUS is symptomatic, consisting in early diagnosis, and usually involving the use of plasmapheresis, dialysis or haemodialysis in case of renal failure. Also, blood transfusions may be necessary in patients with severe anemia and intensive care in critically ill patients.
The American Academy of Pediatrics does not recommend the use of antibiotics and/or anti-diarrheal drugs which inhibit gastric motility, such as loperamide, in infants and children suspected of suffering from infectious gastroenteritis. (In: Pickering L K, ed. Red Book Report of the Committee on Infectious Diseases, 25th ed., Elk Grove Village, 2000).
Previous studies have shown that treatment with antibiotics of an ECEH infection could significantly increase the risk of developing HUS. Bacterial membrane injuries, produced by antibiotics could increase massive release of preformed toxin. In addition, the use of antibiotics might bring about a selective advantage for ECEH over other bacteria which are less resistant to antibiotic therapy, thereby promoting ECEH proliferation.
It has also been demonstrated that certain antibiotics are potent inducers of Shiga toxin gene expression and may cause an increased toxin level in the intestine. Also, STEC strains have shown resistance to third generation cephalosporins and other antibiotics, such as Trimethoprim-Sulfa and Tetracyclines, in addition to being producers of broad-spectrum Beta-lactamases.
Infections by Shiga toxin-producing Escherichia coli strains, a food-borne pathogen in industrialized countries, are the main cause of the high incidence of HUS in Argentine children under 5 years of age.
Argentina has the highest rate of HUS incidence in the world (about 12.5 cases per 100,000 children under 5 years of age), with about 400 new cases per year, which represents the second cause of chronic renal failure (CRF) and of renal transplant indications in our country.
In its update of Jun. 6, 2011, the World Health Organization (WHO) reported the following cases in Germany:                630 HUS cases, 15 of them fatal.        1601 cases of diarrhea caused by enterohaemorrhagic Escherichia coli (ECEH), 6 of them fatal.        
Furthermore, it was reported that the infection spread from Germany to 13 countries, including 12 European Union countries.
Several studies have demonstrated that the infection is foodborne, being bovine faeces the most common source of contamination. The infecting dose is very small, of about 102 CFU. Transmission is by food and water contaminated with bovine faeces and from person to person. US experience shows that lowering contamination of meat during slaughter it is not enough. The latest outbreak vectors have been vegetables contaminated with O157:H7, probably through fertilizers or irrigation water contaminated with bovine faeces. Contact of children with farm animals has also been recognized as a risk factor. All these evidences further support the need of reducing STEC excretion in the pre-slaughter stage.
Appropriate management practices would prevent spreading of pathogenic bacteria among cattle on a farm. It should be kept in mind that while some STEC strains are pathogenic for calves, most of them, including O157:H7, are zoonotic agents which do not affect the health of herds. Preventative measures would thus arise from the need of protecting public health and improving productivity.
Thus, to this date there is no method available for health professionals to prevent and/or treat haemolytic uremic syndrome (HUS).